Biomarkers influence treatment decisions in ovarian cancer

Natalie Godby, DO

Gynecologic Oncologist, City of Hope Atlanta

Genetic markers play an even more important role in ovarian cancer. BRCA1/2 Genetic mutations in many patients. Testing for specific biomarkers not only predicts disease risk factors, but also guides treatment selection in patients with advanced ovarian cancer to maximize survival outcomes.

Targeted therapy with PARP inhibitors initially showed efficacy in patients with BRCA Mutations, but now their benefits are shown BRCA Wild-type disease with homologous recombination deficiency (HRD) is similar, making testing for both these biomarkers important. Originally approved for late-stage therapy, PARP inhibitor therapy has been shown to be beneficial in the early stages of treatment and is now taking on a role as a primary maintenance therapy following the platinum-based chemotherapy frontline. Plays. Studies have shown that these treatments double the duration of progression-free survival (PFS).^1,2

Another targeted therapeutic approach is on the horizon, with mirvetuximab soravtansine-Elahre (antibody-microtubule inhibitor conjugate) in patients with platinum-resistant epithelial ovarian cancer with high expression of folate receptor alpha has received rapid approval for³ Ovarian cancer has a high recurrence rate, so genetic testing using next-generation sequencing (NGS) and other tools is an important way to find clinical trials for patients with recurrent disease.

In an interview with Targeted Oncology^TMsNatalie Godby, M.D., gynecologic oncologist at , City of Hope Atlanta, discussed the current state of advanced ovarian cancer treatment and how oncologists achieve the best outcomes for their patients.

Targeted Oncology: Can you talk about how the field has changed compared to a few years ago?

Godby: Over the past decade, a lot has changed with regards to ovarian cancer. This was when PARP inhibitors were introduced into our community and was a change from conventional chemotherapy. rice field. However, they can now be used as first-line maintenance therapy.we don’t just see them BRCA [mutation] If it is HRD, it is now in the patient’s homologous recombination state because it responds to these PARP inhibitors.

What was the challenge that made the most difference in your practice?

The most recent exam that has impacted us the most is the PRIMA exam. [NCT02655016] and PAOLA-1 trial [NCT02477644]These include PARP inhibitors used as primary maintenance. The idea of ​​maintenance was first introduced with chemotherapy a few years ago and found to work well. It has been shown to have excellent benefits of prolongation.^Four We found that patients had a longer PFS when a PARP inhibitor was used as a second line. So I researched them in the first line settings.

PRIMA investigated the use of niraparib (Zejura) versus placebo in newly diagnosed patients who responded to platinum agents. Median PFS was significantly superior with niraparib compared to placebo: 13 months with niraparib and 8 months with placebo.¹ This is the HRD status and BRCA Status. PAOLA-1 was studied using bevacizumab [Avastin] Maintained at placebo and compared with bevacizumab and olaparib [Lynparza] Newly diagnosed ovarian cancer patients who responded to platinum-based chemotherapy. Greater benefit was seen when PARP inhibitors and bevacizumab were used as maintenance therapy. PFS was shown to be higher in HRD-positive and BRCA-positive patients.² For newly diagnosed patients with ovarian cancer, BRCA HRD status that helps guide us to proper maintenance therapy, not status.

How do you usually determine the order of treatments with or without treatment? BRCA status or not?

When patients are first diagnosed, their BRCA and homologous recombination status are checked. Then, if the patient is a candidate for bevacizumab, they will receive it on an upfront adjuvant basis.Once you get BRCA and HRD testing, this information can be used to determine whether a patient is a candidate for niraparib or olaparib maintenance therapy.

Are there other goals or exams that you think are relevant in this area?

Last year, we received approval for mirvetuximab sorabutansin Jinx, an antibody against the alpha folate receptor.Soraya Trial [NCT04296890] Patients with platinum resistance who had received 1 to 3 prior lines of therapy were studied. These patients are usually difficult to treat. Antibody therapy mirvetuximab showed an objective response rate of 31.7%. This accelerated FDA approval as it was superior to what was seen with other chemotherapies for these platinum-resistant patients.^3,5 It is newer on the market for our patients.

What do you think would be helpful advice for local oncologists who don’t normally treat ovarian cancer?

Ovarian cancer is very difficult. we, [patients] It has been found that 75% to 80% of patients present with end-stage disease and relapse. I would like to find the best treatment because it would be a big deal if it recurred. I recommend reviewing NGS genomic testing with your oncologist because these tests open up treatment options for patients.

It is always recommended to look for clinical trials of immune checkpoint inhibitors in relapsed patients and even those on first-line therapy. [or] Targeted therapy. This is where patients benefit. Clinical trials are always positive for patients.

Is there anything you would like to emphasize with this setting?

I would like to emphasize NGS molecular testing.I do this quite often in City of Hope [Atlanta]I personally have had some patients qualify for clinical trials based on it and have found some treatments. [that] I have a good reaction. Certain patients with ovarian cancer become platinum-resistant, [found a] Three years after being treated based on that molecular test, she is still doing very well.

_References:

_{1. González-Martín A, Pothuri B, Vergote I, etc. PRIMA/ENGOT-OV26/GOG-3012 investigator. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019:381(25):2391-2402.doi:10.1056/NEJMoa1910962}

_{2. Ray-Coquard I, Pautier P, Pignata S, etc. PAOLA-1 investigator. Combination of olaparib and bevacizumab as first-line maintenance therapy for ovarian cancer. N Engl J Med. 2019;381(25):2416-2428.doi:10.1056/NEJMoa1911361}

_{3. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. news release. FDA. November 14, 2022. Accessed April 28, 2023. https://bit.ly/3oUykl8}

_{4. Burger RA, Brady MF, Bookman MA et al. Incorporation of bevacizumab in first-line treatment of ovarian cancer. N Engl J Med2011;365(26):2473-2483. Doi: 10.1056/NEJMoa1104390}

_{5. Matulonis UA, Lorusso D, Oaknin A, etc. Efficacy and safety of mirvetuximab his soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA trial. J Clin Oncol. 2023;41(13):2436-2445). doi:10.1200/JCO.22.01900}